The following includes information that may be useful in understanding various aspects and embodiments of the present disclosure. It is not an admission that any of the information provided herein is prior art, or relevant, to the presently described or claimed inventions, or that any publication or document that is specifically or implicitly referenced is prior art.
Humans and animals are highly susceptible to radiation-induced damage resulting in cellular, tissue, organ and systemic injuries. In accidental radiation exposure, such as a nuclear explosion or a disaster scenario, many victims will suffer from acute radiation syndrome (ARS) to varying degrees. The immediate objectives at a radiation disaster scene are quite different from the radiation treatment of cancer. In such a disaster scenario, early efforts would involve reaching as many afflicted individuals as possible with a treatment that could prolong life, so that victims could be successfully triaged and receive subsequent, in-depth medical care as dictated by their individual condition and afflictions. Another aspect of such an accidental, or intentional, radiation disaster is that any life-saving drugs or treatments would have to be active at protracted time points following the radiation disaster. This requirement is due to the time it would take to mobilize medical staff, drugs/treatments, and equipment to a disaster scene, so that life-saving drugs/treatments could be administered to victims in need.
In addition, radiation-induced damage to cells, tissues, organs and systems can be the result of radiation exposure in the course of a treatment for a disease, such as cancer, or incidental radiation exposure due to a disaster involving release or radiation, such as a nuclear explosion. Over 40% of cancer patients will require radiation therapy during management of their disease. Although radiation therapy improves the survival of a significant number of cancer patients, both acute radiation toxicity (that which manifests during a course of clinical radiotherapy or shortly thereafter), and late toxicity (developing months to years after completion of radiotherapy) compromise overall outcomes for successfully treated cancer patients.
For example, cutaneous T-cell lymphoma (CTCL) accounts for about 4% of all cases of non-Hodgkin lymphoma and is generally characterized in part by malignant proliferation of skin-homing T-helper cells within the outer layer of the epidermis and dermis. The most common subgroup of CTCL is mycosis fungoides (MF). The precise etiology of CTCL is unknown, but genetic, infective and environmental causes have been suggested. The incidence of CTCL increases with age, with an average onset between 50 and 60 years. CTCL is twice as common in men as in women. Although this disease is less prevalent in children, people of all ages can be affected. The initial course of patients with CTCL is usually followed by a progression from limited patches to more generalized patches, plaques, tumors and finally, nodal or visceral involvement. Patients with CTCL are classified according to clinical staging system based on the extent of skin involvement (T-stage), presence of lymph node and visceral involvement (TNM-classification system). The two most common subtypes of CTCL are mycosis fungoides which is often indolent (slow-growing) in early stages, and a more aggressive form called “Sézary syndrome”. Other less common CTCL subtypes include cutaneous CD30 expressing anaplastic large cell lymphoma, panniculitis-like T-cell lymphoma, aggressive CD8 expressing epidermotropic T-cell lymphoma and gamma-delta T-cell lymphoma. Traditional treatment of patients with CTCL may include both topical and systemic therapies. The most common therapies include psoralene plus UVA irradiation (PUVA), total skin electron beam therapy (TSEBT) and topical and systemic chemotherapy.
TSEBT has been used in treatment of CTCL since the 1950's. Total skin electron beam therapy (TSEBT) or partial skin electron beam therapy (PSEBT) is an effective treatment for cutaneous T-cell lymphoma (CTCL) and mycosis fungoides (MF). Conventional total skin electron irradiation (TSEI) for mycosis fungoides (MF) causes radiation toxicity, requiring treatment interruptions that prolong the treatment period, making patient compliance poor. Prolonged overall treatment time can spare tumor cells and lower the chance of a cure, whereas delivering the total radiation dose over a shorter period provides greater radiobiological benefit and gives better tumor control. Conventionally, TSEI is administered on a daily basis (5 days per week), which invariably results in severe radiation-associated toxicity, requiring treatment interruptions and prolonging the total treatment duration. This may reduce the radiobiological efficiency, affecting the final outcome of the treatment and disease-free
Currently, there are agents that can protect cells and tissues from radiation treatments used in cancer, but none have proven to be very effective. In terms of accidental or intentional radiation exposure, there are no known agents that can significantly prolong life when administered at protracted times after radiation exposure to date.